Systemic inflammation mediates the detrimental effects of obesity on asthma control

BACKGROUND: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood. OBJECTIVE: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control. METHODS: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included usingThe Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of more than or equal to 30 kg/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis. RESULTS: FM (12.73 +/- 3.95 versus 18.59 +/- 2.95 versus 27.82 +/- 5.17 kg; p < 0.0001), VFA (65.99 +/- 23.17 versus 93.96 +/- 10.28 versus 123.10 +/- 18.34 cm2; p < 0.0001), PBF (23.86 +/- 7.46 versus 30.74 +/- 5.08 versus 36.21 +/- 6.28 %; p = 0.0003)and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different amonglean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, andIFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p < 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated throughIL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin. CONCLUSION: Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, andIL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future.